aDepression has many environmental causes. This is part 3 of a 3-part series on depression. In part 1 of this series, we deconstructed the fallacious science behind antidepressants. In part 2, we reviewed research pertaining to inflammation, poor diet, nutritional deficiencies, food allergies and intolerances, thyroid disorders, and probiotics. We also looked at head-to-head and adjunctive clinical trials of natural medicines and antidepressants. With the assumption that readers have already viewed this material, I now continue by reviewing research pertaining to stress, trauma, social and lifestyle factors, chronic infections, and toxicants. Lastly, I close with some treatment suggestions.

Table Of Contents

Chronic Infection as a Cause of Depression

A 2014 paper attempted to conceptualize depression as an infectious disease.¹ And indeed, there is a lot more evidence to go on than what they reviewed. Infection is perhaps the most overlooked cause of depression. There are many possible organisms involved. I believe the best thing to do is to develop better methods of empirical treatment. Our organization intends to conduct trials testing electrically isolated silver (a.k.a. colloidal silver) and a poly-herbal preparation in the empirical treatment of infection.

A nationwide study of 3.56 million Danes found that history of hospitalization for infection increased the risk of later having a mood disorder by 62%. History of autoimmunity was also associated with increased risk, and history of autoimmunity and infection interacted in synergy, increasing risk of a mood disorder by a factor of 2.35.² Another nationwide study of over 7 million Danes found that 24.1% of individuals who committed suicide had previously been diagnosed with an infection during a hospitalization. Hospitalization with infection was linked to a 42% increased risk of suicide compared to those without prior infection. The risks further increased with increasing number of infections and increasing length of treatment.³

A meta-analysis selected 28 studies to compare the detection of 16 different infectious organisms in depressed patients compared to controls. Significant association was found for Borna disease virus (BDV), herpes simplex virus-1, varicella zoster virus, Epstein-Barr virus (EBV), and chlamydophila trachomatis. BDV for example had an odds ratio of 3.25.⁴ However, some studies have failed to find an association between BDV and depression.^5–7 Antiviral treatment of BDV-infected depressed or manic patients appeared to produce benefits in a few small trials, though some of them were open-label.⁸ EBV reactivation is also associated with attachment anxiety.⁹

The presence of cytomegalovirus (CMV) IgG antibodies in older adults is associated with depression, anxiety, and overall psychological morbidity.¹⁰ Another study of Detroit residents found that those in the highest quartile of CMV IgG antibodies had nearly 4 times the incidence of depression compared to the lower three quartiles.¹¹

A study found that veterinarians infected with bartonella reported irritability 68% of the time, whereas controls reported irritability 43% of the time.¹² Bipolar depressed patients have been found to have elevated IgG antibodies to Mason-Pfizer monkey virus (MPMV)¹³ West Nile virus may be a cause of depression.¹⁴ Neurocysticercosis (NCC) is an infection of the brain or spinal cord caused by the larval stage of the pork tapeworm, Taenia solium. Between 83% and 100% of patients with NCC have depression.¹⁵

Toxoplasma gondii infection has been associated with suicide and suicide attempt, and a variety of psychiatric disorders including mania, depression, anxiety, schizophrenia, and OCD.^16–23

Anti-Saccharomyces cerevisiae antibodies (ASCA) is a marker of GI inflammation. In one study, an elevated ASCA conferred a 3.5-4.4 fold risk of bipolar disorder. ASCA also correlated with food antibodies in bipolar patients, and with antibodies to measles and T. gondii in patients with recent onset psychosis bipolar disorder.²⁴

Higher levels of antibodies against certain gut bacteria are found in depressed patients relative to controls. This suggests a “leaky gut” in which germs are escaping the intestines. The bacteria could be either the primary cause of the systemic inflammation leading to leaky gut, or they could be a secondary factor which further intensifies systemic inflammation.²⁵

Gum disease is associated with depression.²⁶ While some would say that gum disease is due to depression causing poor dental hygiene, it could partially be just the reverse. Many systemic diseases have been associated with oral infection – a topic I will discuss another time. It could be that the infection exacerbates depression. Or it could be that gum disease is a sign of a systemic disease process, and hence another indication that depression has definite physiological causes.

Depressive states are common in Lyme disease, with psychiatric patients exhibiting higher antibodies to borrelia burgdorferi than controls.^27–30 Bransfield wrote:

“Thousands of peer-reviewed journal articles demonstrate the causal association between infections and mental illness and over 250 peer-reviewed scientific articles demonstrate the causal association between Lyme/tick-borne disease and mental illness.”³¹

In 2017 Bransfield estimated that each year in the USA there are possibly over 1,200 suicides linked with Lyme and associated diseases.^30,32

Sinusitis (i.e. sinus infection) may be a cause of depression, likely due to lost productivity.^33,34

Post-mortem examination has associated active HHV-6 infection with major depression, bipolar disorder, and to a lesser extent schizophrenia.³⁵

Candida Infection as a Cause of Depression

A 2016 study found a link between some psychiatric disorders and Candida infection:

“In males, C. albicans seropositivity conferred increased odds for a schizophrenia diagnosis (OR 2.04–9.53, P ≤0.0001). In females, C. albicans seropositivity conferred increased odds for lower cognitive scores […] in schizophrenia (OR 1.12, P ≤0.004), with significant decreases on memory modules for both disorders (P ≤0.0007–0.03). C. albicans IgG levels were not impacted by antipsychotic medications. Gastrointestinal (GI) disturbances were associated with elevated C. albicans in males with schizophrenia and females with bipolar disorder (P ≤0.009–0.02).”³⁶

A follow-up RCT found that probiotic supplementation reduced yeast antibodies in males. There was also an observed trend towards improvement in positive psychiatric symptoms in males who were seronegative for Candida.³⁷

We do know Candida overgrowth can occur even in apparently health individuals.³⁸ Could Candida also be linked to depression? We do know that psoriasis has been linked in multiple studies to both depression and Candida infection. (See Appendix.) Could some depression experienced by some patients with psoriasis be due to Candida?

Candida infection may also be a trigger of celiac disease, which I have already discussed is linked to depression.^39,40

As I mention later on, oral contraceptives have been linked to depression. Observational studies have also found an association between use of oral contraceptives and Candida. And estrogen has been observed to regulate the virulence of Candida. (See Appendix.) Could oral contraceptives cause depression by exacerbating a Candida infection?

Similarly, proton-pump inhibitors have been linked to both depression and Candida infection, with known mechanisms by which they may predispose one to Candida. (See Appendix.)

Antibiotics are known to increase risk of Candida infection. And antibiotic use is associated with depression.⁴¹

And since sugar can exacerbate the virulence of an existing Candida infection, causing it to change from an oval form to an infectious filamentous form (see Appendix), could a Candida hypothesis explain the anecdotal worsening of symptoms after ingesting sugar or carbs noted by some depressed individuals? Might Candida even have a means of inducing carbohydrate cravings?⁴² I have already discussed that processed food dietary patterns and high glycemic index diets are associated with depression and schizophrenia. Could it be that these diets provide more sugar to fuel a Candida infection? Could this even explain some of the link between alcohol and depression on account of the fact that Candida can use not only glucose, but also ethanol to produce toxic acetaldehyde in the gut where it usually would not occur? (See Appendix.)

We know there is a rationale for glucose restriction in treating Candida.⁴³ Could it be that the anecdotal flu-like symptoms some patients have from avoidance of sugar and refined carbohydrates are actually Jarisch-Herxheimer reactions (JHRs) due to a dying Candida infection? For example, low-carbohydrate diets have been popularly associated with causing “keto flu”.⁴⁴ Individuals who experience sensitivity to coconut oil (an antifungal⁴⁵) may also actually be experiencing a JHR. I define and discuss JHRs in the next section. The same may be true of baking soda, another antifungal which has fever and chills among the most commonly reported reactions.⁴⁶ Similarly, flu-like symptoms such as fever and chills are among the most common reported reactions to glucose. Could these be due to aggravation of a Candida infection?

Some consider chronic Candida to be a dubious diagnosis partially on account of the fact that nystatin apparently does not benefit women who fit the description.⁴⁷ This study has a number of issues however. It only had 42 people. They were also rotated between treatment combinations without any washout periods. The authors arguably did report some possible systemic benefits, but reasoned them away too hastily in my opinion. They also did nothing to address potential herx reactions (discussed in the next section) which can cause worsening of symptoms prior to realizing net improvements. There was also no control over gluten, sugar, or alcohol intake. Lastly, it is also possible that nystatin simply doesn’t work. It is not absorbed systemically, and Candida can be systemic, though it may start in the intestines. We need to test other antifungals such as coconut oil and oregano oil. These combination antifungals also need to be coupled with sugar, alcohol, and gluten avoidance and probiotic supplementation to maximize chance of success. The authors themselves called for more controlled studies.

This is an example of why I say people are failing to understand what I call environmental etiological entanglement. You can’t separate one environmental cause of disease from another, as they can all aggravate one another. In this instance, poor diet may exacerbate infection. Plausible hypotheses are being dismissed as quackery, when the truth is that trials which test interventions in isolation are often naive. This is why our organization is aiming to conduct relatively complex multi-interventional clinical trials that account for these issues.

Failure to account for such entanglement can even lead to counterproductive results. For example fluconazole may actually cause a future Candida infection, which is the opposite of its intended use.⁴⁸ This probably could have been prevented had other interventions been put in place.

Aside from looking for a link between depression and Candida, there is also a need for studies that look for an association with a number of other factors such as history of antifungal use, oral and esophageal thrush, and vaginal thrush. All of these could potentially initiate or indicate Candidiasis of the intestines. Such studies should account for potential time delays, as was done in the above fluconazole study.

The Jarisch-Herxheimer Reaction – An Indication of Chronic Infection

A study of over 60,000 patients with H. pylori treated using clarithromycin found the drug is associated with increased risk of neuropsychiatric events, psychotic events, and cognitive impairment.⁴⁹ In a study of 45 patients who reported adverse events after taking fluoroquinolones, 78% of them reported symptoms that were classified as CNS-related. These included psychiatric symptoms such as nightmares, agitation, anxiety, panic attacks, disorientation, cognitive impairment, depersonalization, hallucinations, and psychoses.⁵⁰ This phenomenon of having reactions to anti-infectives is more pervasive than people realize, and in our opinion these are – in part – actually examples of Jarisch-Herxheimer reactions (JHR or simply “herx”). JHRs are a sign of infectious die-off, caused by a transient spike in biotoxins released by dead microorganisms, and by resulting inflammatory cytokines. I discuss JHRs in more detail in our article reviewing the safety of dietary supplements and alternative therapies. I also discuss the possibility that many anti-infective side effects may actually be JHRs. Hence, I suggest that neuropsychiatric events resulting from antibiotics support a hypothesis that psychiatric disorders can have an infectious etiology.

The JHR is a safety concern especially in those who are frail and in those prone to suicide and violence. Also, driving while under the influence of a JHR may be a safety concern. Patients and clinicians embarking on any form of anti-infective therapy must be aware of the potential for JHRs, and be prepared for it. Even simply avoiding sugar or alcohol could potentially precipitate a JHR, and hence patients that encounter such an event should understand that they are passing through a healing crisis. The overall best way to deal with potential JHRs is to employ ramping of relevant therapies. I discuss this method in more detail in the above-mentioned article on the safety of supplements.

Stress, Trauma, and Lifestyle Factors as a Cause of Depression

Depression may in large part be due to the fact that the world we live in is simply dysfunctional in many senses. Some would argue that not being depressed in a world like this could be considered abnormal in many individuals. Depression may also often be an expected response to stressful life events.

Interpersonal Factors, Trauma, and Life Events

A 2013 study of over 32,000 people found that the single largest determinate of depression and anxiety among those which they studied was traumatic life events. Other lesser determinates included income and education levels, relationship status, and other social factors. The researchers found that these relationships were strongly meditated by psychological processes such as a lack of adaptive coping, rumination, and self-blame.⁵¹ An earlier 1998 survey examined 7 categories of adverse childhood experiences. Respondents who reported experiences in 4 or more categories had a 4.6-fold odds of experiencing depression in the past year, and a 12.2-fold odds of ever having attempted suicide.⁵²

In a study of over 3,400 men and women, people living alone had a 1.81-fold higher purchase rate of antidepressants during the follow-up period compared to people not living alone.⁵³

A study of 4,739 people found that happiness is contagious, that happiness and unhappiness are found in clusters, and that the relationship between people’s happiness extends for up to 3 degrees of separation.⁵⁴

Spouses of those who suffer a heart attack are at increased risk of depression.⁵⁵

Nearly one-quarter of hospice caregivers are moderately to severely depressed, and nearly one-third experience moderate to severe symptoms of anxiety.⁵⁶

Bad relationships are also a risk factor for depression.⁵⁷ As is breakup of romantic relationships.⁵⁸

A study by the Institute of Economic Affairs found retirement was associated with a 40% increased chance of depression.⁵⁹ However, another study associated retirement with a decreased chance of depression.⁶⁰ Perhaps it is what you do or who you are with during retirement that affects your depression risk either positively or negatively?

Multiple studies have found that there is an inverse relationship between eating family meals and mental disorders in adolescents.^61,62

Both late-night texting and “hyper-texting” have been associated with depression, as well as a wide variety of other adverse traits. Though determining causal relationships is very muddy. Lack of good sleep due to staying up too late, emotional and cognitive arousal, and blue-light exposure are notable likely causal pathways.^63,64

Thirty-six percent of depressed individuals have been estimated to have PTSD (post-traumatic stress disorder), and 52% of those with PTSD have been estimated to have depression.^65,66

Job loss is associated with depression.⁶⁷

Both adolescent bullies and bully victims are at increased risk of depression.⁶⁸

Lack of social support or concerns over child health and development are possible causes of postpartum depression.⁶⁹

Adopting a pet may effectively treat depression.⁷⁰

Urbanization, Gardening, and Nature

Urbanization is associated with increased depression. Healthy individuals who took a 90-minute walk in nature showed decreases in both self-reported rumination and neural activity in the subgenual prefrontal cortex, whereas individuals who took a walk in an urban setting did not.⁷¹ A 50-minute walk in nature increased memory span and mood in depressed patients, relative to taking a walk in an urban setting.⁷² Another study found that city living and urban upbringing adversely affect neural social stress processing in humans.⁷³ The authors also note that previous work found that city dwellers have a 21% increased chance of anxiety disorders and 39% increased chance of mood disorders.⁷⁴

A 2016 meta-analysis found that gardening is consistently reported as an effective intervention in depression and anxiety, as well as in a variety of other health outcomes.⁷⁵

Exposure to nature is an important factor in depression. (Note that a lack of gardening and the presence of urban surrounding can both be conceptualized as a lack of access to nature.) Living with greater visibility of bodies of water such as lakes and oceans is associated with lower psychological distress.⁷⁶ Self-reported connectedness to nature is associated with lower anxiety.⁷⁷ The first systemic review to look at the health benefits of living in a green space was published in 2015 and found green space is associated with improved perception of mental health, and a reduction in all-cause mortality.⁷⁸ A 2016 study largely replicated these results, but also found that blue space is associated with lower anxiety and mood disorders, and higher self-reported mental and general health.⁷⁹ A meta-analysis of 10 studies found that exercising in green environments leads to improvements in self-esteem and mood.⁸⁰

Other references on green spaces: 10.1021/es403688w, PMC4410252 .

Altitude is correlated with suicide. (PMC4643668, PMC3114154)

One mechanism by which nature may provide health benefits is through supplying negative air ions. Negative air ion therapy may be effective in depression.
https://www.ncbi.nlm.nih.gov/pubmed/29024857
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598548/

Exercise

Multiple reviews have found that exercise appears to be an effective intervention, both as a standalone and as an adjunct.⁸¹ One important consideration is that in many trials the control intervention may actually have benefit beyond that of a placebo. Examples of such control interventions include talking on the phone about their health, relaxation, and meditation. Hence, benefits of exercise may be more meaningful than meets the eye.

A large prospective cohort study of healthy adults concluded “Regular leisure-time exercise of any intensity provides protection against future depression but not anxiety.”⁸² Response to exercise may be influenced by age and severity of depression, with aerobic exercise generally being more beneficial than strength training.⁸³ Depending on gender and family history, different intensities of exercise may be optimal, with high-intensity exercise generally appearing to give better results than lower-intensity exercise.⁸⁴ A 2013 review found that yoga has Grade B evidence supporting a potential benefit in the treatment of depression.⁸⁵

Spirituality

Belief in God, but not religious affiliation, is associated with better treatment outcomes among depressed patients.⁸⁶ Another study found an association between spirituality and mental health. The researchers suggest that health care providers should take use of this relation and tailor treatments to accommodate an individual’s spiritual inclination.⁸⁷

Emotional Suppression

One study found that suppressing positive emotions may contribute to postpartum depression.⁸⁸ Whereas other research tends to focus on a poor response to stressful events, this study suggests that a poor response to positive events may also play a role in depression.

Acceptance of negative thoughts and emotions is a predictor of better psychological health, including depressive symptoms.⁸⁹

Retrospective studies have shown that crying is beneficial for mood. However, quasi-experimental laboratory studies show that crying worsens mood in the immediate timeframe. A 2015 study possibly explained this discrepancy. Researchers found that people who cry immediately after an emotional movie have deteriorations in their moods when measured 20 minutes later, but after 90 minutes they exhibit mood enhancements beyond baseline measurements.⁹⁰ So it appears that crying is therapeutic and could be essential for those suffering for depression. It becomes especially of concern when we recall that 60% of patients on antidepressants report feeling, “emotionally numb”.⁹¹ I suspect that antidepressants are actually interfering with a normal process of emotional release, which could be part of the reason why they make depression worse.

Facebook, Cell Phone, and Internet Use

A variety of studies and systematic reviews have looked at the effect of Facebook and social media use on mental health.^92,93 Overall, the results are mixed, suggesting that sometimes social media can worsen mood and sometimes it can improve it, depending on the context. One context appears to be when people log on with the expectation of feeling better. When their expectations are not met, they make themselves feel worse. Another negative context is that people feel they wasted their time. Another is when an individual is prone to social comparison and developing envy. Another is when people view content that is negative in nature such as corruption and environmental destruction. And another context is when people feel bullied or criticized.

A 2016 study conducted a one-week controlled experiment where people either discontinued or continued using Facebook. Those who discontinued use reported increased life satisfaction and positive emotions. These results were greater for heavy Facebook users, passive Facebook users, and users who tend to envy others on Facebook.⁹⁴ A 2017 study of 5,208 subjects found that overall, facebook use is negatively associated with well-being.⁹⁵

Cell phone and internet use have been found to negatively contribute to depression and anxiety as well as a number of other factors such as relationship satisfaction.^96,97

Overworking and Negative Work Environment Factors

Working overtime 11 hours a day as compared to 7 or 8 hours a day is associated with a 2.43-fold risk of depression.⁹⁸ A study of 5,575 school teachers found that 90% of teachers identified as “burned out” met the diagnostic criteria for depression.⁹⁹ A study of 8,000 Australian adults found that beyond an average of a 39-hour work week, mental health starts to decline.¹⁰⁰ Job strain, bullying, and a lack of decision latitude at work have also been associated with depression. (See Appendix).

Sleep and Circadian Rythm Disorders

Sleep disturbance may cause depression.¹⁰¹ Increases in sleep duration and sleep quality are associated with improvements in mental health scores.¹⁰² Circadian misalignment and melatonin secretion has been linked to depression in a number of studies. And those who go to bed the latest have almost twice the odds of psychological disorder than those who sleep the earliest. (See Appendix). In comorbid cases of insomnia and depression, insomnia precedes the depression 69% of the time in youth.¹⁰³ However, supplementation with melatonin has not led to clear benefits in depression or seasonal affective disorder.^104,105 A head-to-head trial found that light therapy outperformed fluoxetine (Prozac).¹⁰⁶ Other studies suggest light therapy may be of benefit in seasonal affective disorder.^107–109 Though another small study did not find benefit from phototherapy.¹¹⁰ Multiple studies suggest that treating comorbid insomnia increases remission rates in depressed patients. This usually involves tweaking cognitive behavioral therapy towards addressing insomnia specifically.^111,112 Other studies suggest that sleep apnea appears to be a cause of depression, and that treating apnea with CPAP therapy leads to improvements in depression scores.^113,114

Music

A meta-analysis found that music may alleviate depressive symptoms.¹¹⁵

Meditation and Related Activities

Several meta-analyses have concluded that mindfulness meditation is beneficial in the treatment of psychological problems including depression, anxiety, and stress. (See Appendix.) However, research is confounded by publication biases, other reporting biases, a lack of a standard definition, and inadequate control, potentially causing overestimation of benefits.^116,117 Yet it is notable that studies that use the more convincing types of controls (such as a specific active control or another evidence-based therapy) still suggest benefit. A 2016 study found that meditation combined with aerobic exercise improves symptoms of depression, possibly more than either or the two activities alone.¹¹⁸ A review and meta-analysis of tai chi found that it may be effective in the treatment of depression.¹¹⁹ A study found 10 weeks of group drumming was associated with significant decreases in depression, whereas the control group had no significant decrease. The drumming group also showed measurable improvements in markers of inflammation.¹²⁰

A study took 39 family dementia caregivers with depressive symptoms and randomized them to either practice a meditation called Kirtan Kriya, or listen to relaxation music as a control. The results stated:

In the meditation group, 65.2% showed 50% improvement on the Hamilton Depression Rating scale and 52% of the participants showed 50% improvement on the Mental Health Composite Summary score of the Short Form-36 scale compared with 31.2% and 19%, respectively, in the relaxation group (p < 0.05). The meditation group showed 43% improvement in telomerase activity compared with 3.7% in the relaxation group (p = 0.05). ¹²¹

Brogan recommends this method of meditation and reports that it has been indispensable in her practice.¹²²

Recap

In short, there are a lot of things about the way we live and the world we live in that are conducive to depression. Overall, it seems that a healthy life is one that involves a combination of nature, sunlight (was reviewed in part 2), emotional expression, exercise, being around other people that you like and that treat you well, spirituality, meditation, regulated use of internet and cell phones, rest, attention to sleep issues, and potentially even avoidance of blue light and other man-made EMFs.

Toxicants as a Cause Depression

Numerous toxicants have been implicated as causes of depression.

Multiple Chemical Sensitivity

A study of 400 patients recruited from the waiting rooms of two family clinics found that a remarkable 20% of patients met the criteria for chemical intolerance (i.e. multiple chemical sensitivity). Among people who were found to be chemical intolerant, a startling 85% reported having symptoms of major depression within the last month, and 78% symptoms of anxiety disorder. That compared with only 33% and 21% in the non-chemical intolerant group respectively. Among people found to be sensitive, only 25% had been previously diagnosed with chemical intolerance.¹²³ This could indicate a need to reduce chemical exposures, or it might be that sensitivities are a result of other underlying causes.

Mold

Living in damp and moldy homes has been associated with depression.¹²⁴

Aspartame

Patients with mood disorders appear to be especially vulnerable to adverse reactions from aspartame, with one study having to be halted by a review board.¹²⁵

Mercury Fillings

A 2014 review concludes that evidence supports the links between mercury fillings and many diseases, including depression.¹²⁶ A 1994 study linked mercury fillings in women to depression, fatigue, insomnia, anger, and anxiety. Twenty-five women with mercury fillings exhibited more of these symptoms than did 23 women without fillings.¹²⁷ A 2006 study of hundreds of patients diagnosed with chronic mercury toxicity found that about 28% of them suffered depression, and that the depression typically resolved after removal of mercury fillings and accompanying mercury detoxification therapies.¹²⁸ A study of self-referred patients who attributed their mental problems to mercury fillings found that 47% reported major depression, whereas between 0% to 14% of controls reported major depression.¹²⁹ However, confirmation bias presumably slants this study. Another study found that multiple sclerosis patients with mercury fillings have more depression than those who have their fillings removed.¹³⁰

Mercury from other sources are also a concern.¹³¹ For example occupational exposure to mercury is associated with depression.¹³²

While there are still many who claim that mercury fillings are safe, most studies in support of this claim are severely flawed.¹³³

Lead Poisoning and Smoking, and Other Substances

Lead exposure has been associated with depression as well as a variety of psychopathologies.¹³⁴

Many studies have associated smoking with increased risk of depression and suicide.^135–140 I wonder if part of the explanation could be an induced lead poisoning, which may occur with both first-hand and second-hand smoke.^141,142 A 2014 systematic review and meta-analysis concluded:

“Smoking cessation is associated with reduced depression, anxiety, and stress and improved positive mood and quality of life compared with continuing to smoke. The effect size seems as large for those with psychiatric disorders as those without. The effect sizes are equal or larger than those of antidepressant treatment for mood and anxiety disorders.”¹⁴³

Pesticides

Several studies have linked pesticide use among farm residents to depression and suicide.^144–151

Air and Noise Pollution

Air pollution has been associated with anxiety and psychological stress, though other forms of pollution such as noise could explain these results.^152,153 And indeed, traffic and other noise sources are linked to depression.^154,155

Bisphenol A

Prenatal BPA exposure is associated with depression and anxiety in boys, but not girls, at ages 10-12.¹⁵⁶

Pharmaceutical Drugs

Prescription drugs can also be conceptualized as toxicants.

In one study of nearly 50,000 veterans, opioid pain-killers were associated with a 25% increased chance of depression, after adjusting for symptoms of pain. One explanation is that the drugs may reset the brain’s reward pathway to make it more difficult to experience pleasure from natural rewards like food.¹⁵⁷

Some blood pressure drugs (calcium antagonists and beta-blockers) may also affect the development of depression, and increase the risk of depression severe enough to require hospitalization.^158,159 Lipophilic beta-blockers have also been linked to suicide in the elderly.¹⁶⁰

Oral contraceptives are associated with increased first use of an antidepressant. Depending on the age of the women, the contraceptive(s) used, and the duration of use, average increased chances range from 23% to 120%.¹⁶¹ As I have already discussed, exacerbation of Candida infection may be one of multiple mechanisms by which oral contraceptives cause depression. Contraceptives have likewise been linked to increased risk of suicide and suicide attempt.¹⁶²

Proton-pump inhibitors have been linked to depression. (See Appendix.) Again, I have already discussed exacerbation of Candida as a possible mechanism.

A 2013 review concluded that statins may cause depression.¹⁶³ A number of studies have found an association between low cholesterol and violence, suicide, depression, anxiety, and bipolar disorder.^164–167 This could be in part due to statin therapy.

As we have already seen, antibiotic use is associated with depression.⁴¹

A 2018 cross-sectional survey study found that polypharmacy is associated with depression. More than 200 commonly prescribed drugs have depression as a possible side effect, and the greater number of drugs one takes, the more likely one is to be depressed.¹⁶⁸ Although the direction(s) of causality are unclear and there may be some other explanations for this association, those with depression should always reflect on a potential role of current prescribed and over-the-counter medications.

Artificial Light and Man-Made EMFs as Toxicants

Evening exposure to blue light from artificial light sources may disturb mood, and wearing blue-light blocking glasses may benefit bipolar patients.¹⁶⁹ Low-level exposure to light at night has also been associated with depression.^170–172 Many studies have found that a number of other sources of man-made EMFs have been associated with neuropsychiatric effects, including depression, with several criteria being met to demonstrate causality.¹⁷³

So What Should I Actually Do to Treat Depression?

With so much research about the complex causes of depression, what should a patient or physician actually do? Though each person is unique, I suggest the following as a starting point of investigation and effort:

Get social support. This could be supportive friends or family, health professionals, or online forums or communities. Many are disillusioned with antidepressants and “treatment as usual”, and so people are certainly not alone. If you experience self-harm, suicidal thoughts, have had suicide attempts, or if you may in any sense be at risk of suicide, strongly consider seeking cognitive behavioral therapy, which (unlike antidepressants) does have credible evidence that it can cut suicide attempts in half.¹⁷⁴
Do not make any changes to antidepressant dosage at present. If you are not on antidepressants, don’t start any. Aim to feel better before even considering tapering off of a drug with the help of a physician.
Eliminate all refined sugar, refined carbohydrates, processed foods, fruit juices (whole fruits are encouraged), alcohol, gluten, and dairy for one entire month. Make a food plan. Be aware of the possibility of a herx reaction (JHR). After one month, do whatever you want. Give yourself the chance to observe how the reintroduction of these foods does or does not affect your mood.
Only after stabilizing on this diet, introduce probiotics and raw coconut oil, one at a time. Again, be aware of the possibility of a JHR. At the date of writing this, I recommend Epic Pro probiotics sold by Swanson Vitamins. They also sell coconut oil. Probiotics are best used by opening the capsules, dispersing in water, and drinking on empty stomach. Another cost-effective source of probiotics is homemade fermented vegetables.
Start a daily 5-minute meditation practice. Choose one from those I reviewed, or feel free to look into other practices, especially those associated with any religious background you might have.
Exercise outside daily. Ideally, this should be done in nature.
Reflect on current prescription and over-the-counter medications that may have depression as a side effect.

These suggestions bear some similarity to those given by Brogan in her book, A Mind of Your Own.¹⁷⁵

And of course, read the disclaimer at the bottom of the website.

Conclusion – Antidepressants are Terrible, Depression Has Complex Environmental Causes

Modern medicine has done many good things for society. Antidepressants are not one of them. They are a textbook example of how an entire scientific community can become completely lost in the fabricated narratives of a corrupt industry, and in their own echo chambers.

Thankfully, there is a way out. Natural and environmental medicine offer many sensible avenues for the treatment of depression. Unlike the quick fix of a prescription, these paths require effort, investigation, and self-awareness. Aside from potential health improvements, many will find such an involved process of healing to be inherently rewarding and eye-opening.

Canli T. Reconceptualizing major depressive disorder as an infectious disease. Biol Mood Anxiety Disord. 2014;4:10. [PubMed]

Benros M, Waltoft B, Nordentoft M, et al. Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study. JAMA Psychiatry. 2013;70(8):812-820. [PubMed]

Lund-Sørensen H, Benros M, Madsen T, et al. A Nationwide Cohort Study of the Association Between Hospitalization With Infection and Risk of Death by Suicide. JAMA Psychiatry. 2016;73(9):912-919. [PubMed]

Wang X, Zhang L, Lei Y, et al. Meta-analysis of infectious agents and depression. Sci Rep. 2014;4:4530. [PubMed]

Iwata Y, Takahashi K, Peng X, et al. Detection and sequence analysis of borna disease virus p24 RNA from peripheral blood mononuclear cells of patients with mood disorders or schizophrenia and of blood donors. J Virol. 1998;72(12):10044-10049. [PubMed]

Hornig M, Briese T, Licinio J, et al. Absence of evidence for bornavirus infection in schizophrenia, bipolar disorder and major depressive disorder. Mol Psychiatry. 2012;17(5):486-493. [PubMed]

Na K, Tae S, Song J, Kim Y. Failure to detect borna disease virus antibody and RNA from peripheral blood mononuclear cells of psychiatric patients. Psychiatry Investig. 2009;6(4):306-312. [PubMed]

Dietrich D, Bode L. Human Borna disease virus-infection and its therapy in affective disorders. APMIS Suppl. 2008;(124):61-65. [PubMed]

Fagundes C, Jaremka L, Glaser R, et al. Attachment anxiety is related to Epstein-Barr virus latency. Brain Behav Immun. 2014;41:232-238. [PubMed]

10.

Phillips A, Carroll D, Khan N, Moss P. Cytomegalovirus is associated with depression and anxiety in older adults. Brain Behav Immun. 2008;22(1):52-55. [PubMed]

11.

Simanek A, Cheng C, Yolken R, Uddin M, Galea S, Aiello A. Herpesviruses, inflammatory markers and incident depression in a longitudinal study of Detroit residents. Psychoneuroendocrinology. 2014;50:139-148. [PubMed]

12.

Lantos P, Maggi R, Ferguson B, et al. Detection of Bartonella species in the blood of veterinarians and veterinary technicians: a newly recognized occupational hazard? Vector Borne Zoonotic Dis. 2014;14(8):563-570. [PubMed]

13.

Dickerson F, Katsafanas E, Schweinfurth L, et al. Immune alterations in acute bipolar depression. Acta Psychiatr Scand. 2015;132(3):204-210. [PubMed]

14.

Berg P, Smallfield S, Svien L. An investigation of depression and fatigue post West Nile virus infection. S D Med. 2010;63(4):127-129, 131-133. [PubMed]

15.

Almeida S, Gurjão S. Frequency of depression among patients with neurocysticercosis. Arq Neuropsiquiatr. 2010;68(1):76-80. [PubMed]

16.

Sutterland A, Fond G, Kuin A, et al. Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis. Acta Psychiatr Scand. 2015;132(3):161-179. [PubMed]

17.

Hsu P, Groer M, Beckie T. New findings: depression, suicide, and Toxoplasma gondii infection. J Am Assoc Nurse Pract. 2014;26(11):629-637. [PubMed]

18.

Dalimi A, Abdoli A. Latent Toxoplasmosis and Human. Iran J Parasitol. 2012;7(1):1-17. [PMC]

19.

Markovitz AA, Simanek AM, Yolken RH, et al. Toxoplasma gondii and anxiety disorders in a community-based sample. Brain, Behavior, and Immunity. 2015;43:192-197. doi:10.1016/j.bbi.2014.08.001

20.

Dickerson F, Stallings C, Origoni A, et al. A combined marker of inflammation in individuals with mania. PLoS One. 2013;8(9):e73520. [PubMed]

21.

Lester D. Brain parasites and suicide. Psychol Rep. 2010;107(2):424. [PubMed]

22.

Zhang Y, Träskman-Bendz L, Janelidze S, et al. Toxoplasma gondii immunoglobulin G antibodies and nonfatal suicidal self-directed violence. J Clin Psychiatry. 2012;73(8):1069-1076. [PubMed]

23.

Henriquez S, Brett R, Alexander J, Pratt J, Roberts C. Neuropsychiatric disease and Toxoplasma gondii infection. Neuroimmunomodulation. 2009;16(2):122-133. [PubMed]

24.

Severance E, Gressitt K, Yang S, et al. Seroreactive marker for inflammatory bowel disease and associations with antibodies to dietary proteins in bipolar disorder. Bipolar Disord. 2014;16(3):230-240. [PubMed]

25.

Maes M, Kubera M, Leunis J, Berk M. Increased IgA and IgM responses against gut commensals in chronic depression: further evidence for increased bacterial translocation or leaky gut. J Affect Disord. 2012;141(1):55-62. [PubMed]

26.

Sundararajan S, Muthukumar S, Rao S. Relationship between depression and chronic periodontitis. J Indian Soc Periodontol. 2015;19(3):294-296. [PMC]

27.

Fallon B, Nields J. Lyme disease: a neuropsychiatric illness. Am J Psychiatry. 1994;151(11):1571-1583. [PubMed]

28.

Tager F, Fallon B, Keilp J, Rissenberg M, Jones C, Liebowitz M. A controlled study of cognitive deficits in children with chronic Lyme disease. J Neuropsychiatry Clin Neurosci. 2001;13(4):500-507. [PubMed]

29.

Hájek T, Pasková B, Janovská D, et al. Higher prevalence of antibodies to Borrelia burgdorferi in psychiatric patients than in healthy subjects. Am J Psychiatry. 2002;159(2):297-301. [PubMed]

30.

Bransfield R. Neuropsychiatric Lyme Borreliosis: An Overview with a Focus on a Specialty Psychiatrist’s Clinical Practice. Healthcare (Basel). 2018;6(3):104. [PMC]

31.

Bransfield R. The Psychoimmunology of Lyme/Tick-Borne Diseases and its Association with Neuropsychiatric Symptoms. Open Neurol J. 2012;6:88-93. [PMC]

32.

Bransfield R. Suicide and Lyme and associated diseases. NDT. 2017;Volume 13:1575-1587. doi:10.2147/ndt.s136137

33.

Campbell AP, Phillips KM, Hoehle LP, et al. Depression symptoms and lost productivity in chronic rhinosinusitis. A. 2017;118(3):286-289. doi:10.1016/j.anai.2016.12.012

34.

Kim J-Y, Ko I, Kim MS, Yu MS, Cho B-J, Kim D-K. Association of Chronic Rhinosinusitis With Depression and Anxiety in a Nationwide Insurance Population. J. 2019;145(4):313. doi:10.1001/jamaoto.2018.4103

35.

Prusty BK, Gulve N, Govind S, et al. Active HHV-6 Infection of Cerebellar Purkinje Cells in Mood Disorders. F. 2018;9. doi:10.3389/fmicb.2018.01955

36.

Severance EG, Gressitt KL, Stallings CR, et al. Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder. NPJ Schizophr. 2016;2:16018. doi:10.1038/npjschz.2016.18

37.

Severance E, Gressitt K, Stallings C, et al. Probiotic normalization of Candida albicans in schizophrenia: A randomized, placebo-controlled, longitudinal pilot study. Brain Behav Immun. 2017;62:41-45. [PubMed]

38.

Martins N, Ferreira I, Barros L, Silva S, Henriques M. Candidiasis: predisposing factors, prevention, diagnosis and alternative treatment. Mycopathologia. 2014;177(5-6):223-240. [PubMed]

39.

Nieuwenhuizen W, Pieters R, Knippels L, Jansen M, Koppelman S. Is Candida albicans a trigger in the onset of coeliac disease? Lancet. 2003;361(9375):2152-2154. [PubMed]

40.

Corouge M, Loridant S, Fradin C, et al. Humoral immunity links Candida albicans infection and celiac disease. PLoS One. 2015;10(3):e0121776. [PubMed]

41.

Lurie I, Yang Y, Haynes K, Mamtani R, Boursi B. Antibiotic exposure and the risk for depression, anxiety, or psychosis: a nested case-control study. J Clin Psychiatry. 2015;76(11):1522-1528. [PubMed]

42.

Wurtman R, Wurtman J. Brain serotonin, carbohydrate-craving, obesity and depression. Obes Res. 1995;3 Suppl 4:477S-480S. [PubMed]

43.

Vargas SL. Modulating effect of dietary carbohydrate supplementation on Candida albicans colonization and invasion in a neutropenic mouse model. American Society for Microbiology | Infection and Immunity. https://iai.asm.org/content/61/2/619/article-info. Published February 1, 1993. Accessed August 13, 2019.

44.

Campos, MD M. What is keto flu? Harvard Health Blog. https://www.health.harvard.edu/blog/what-is-keto-flu-2018101815052. Published October 18, 2018. Accessed July 19, 2019.

45.

Gunsalus KTW, Tornberg-Belanger SN, Matthan NR, Lichtenstein AH, Kumamoto CA. Manipulation of Host Diet To Reduce Gastrointestinal Colonization by the Opportunistic PathogenCandida albicans. Mitchell AP, ed. mSphere. 2015;1(1):e00020-15. doi:10.1128/msphere.00020-15

46.

VigiAccess. VigiAccess. http://www.vigiaccess.org/. Accessed August 17, 2017.

47.

Dismukes W, Wade J, Lee J, Dockery B, Hain J. A randomized, double-blind trial of nystatin therapy for the candidiasis hypersensitivity syndrome. N Engl J Med. 1990;323(25):1717-1723. [PubMed]

48.

Tyczkowska-Sieron E, Gaszynski W, Tyczkowski J, Glowacka A. Analysis of the relationship between fluconazole consumption and non-C. albicans Candida infections. Med Mycol. 2014;52(7):758-765. [PubMed]

49.

Wong A, Wong I, Chui C, et al. Association Between Acute Neuropsychiatric Events and Helicobacter pylori Therapy Containing Clarithromycin. JAMA Intern Med. 2016;176(6):828-834. [PubMed]

50.

Cohen J. Peripheral neuropathy associated with fluoroquinolones. Ann Pharmacother. 2001;35(12):1540-1547. [PubMed]

51.

Kinderman P, Schwannauer M, Pontin E, Tai S. Psychological processes mediate the impact of familial risk, social circumstances and life events on mental health. PLoS One. 2013;8(10):e76564. [PubMed]

52.

Felitti VJ MD, FACP, Anda RF MD, MS, Nordenberg D MD, et al. Relationship of Childhood Abuse and Household Dysfunction to Many of the Leading Causes of Death in Adults. A. 1998;14(4):245-258. doi:10.1016/s0749-3797(98)00017-8

53.

Pulkki-Råback L, Kivimäki M, Ahola K, et al. Living alone and antidepressant medication use: a prospective study in a working-age population. BMC Public Health. 2012;12:236. [PubMed]

54.

Fowler J, Christakis N. Dynamic spread of happiness in a large social network: longitudinal analysis over 20 years in the Framingham Heart Study. BMJ. 2008;337:a2338. [PubMed]

55.

Fosbøl E, Peterson E, Weeke P, et al. Spousal depression, anxiety, and suicide after myocardial infarction. Eur Heart J. 2013;34(9):649-656. [PubMed]

56.

Parker O, Washington K, Smith J, Uraizee A, Demiris G. The Prevalence and Risks for Depression and Anxiety in Hospice Caregivers. J Palliat Med. December 2016. [PubMed]

57.

Teo A, Choi H, Valenstein M. Social relationships and depression: ten-year follow-up from a nationally representative study. PLoS One. 2013;8(4):e62396. [PubMed]

58.

Mearns J. Coping with a breakup: negative mood regulation expectancies and depression following the end of a romantic relationship. J Pers Soc Psychol. 1991;60(2):327-334. [PubMed]

59.

Mercola J. Retirement Increases Your Risk of Depression by 40 Percent. Mercola.com. http://articles.mercola.com/sites/articles/archive/2013/05/30/retirement.aspx. Published May 30, 2013. Accessed February 7, 2017.

60.

Westerlund H, Vahtera J, Ferrie J, et al. Effect of retirement on major chronic conditions and fatigue: French GAZEL occupational cohort study. BMJ. 2010;341:c6149. [PubMed]

61.

Utter J, Denny S, Peiris-John R, Moselen E, Dyson B, Clark T. Family Meals and Adolescent Emotional Well-Being: Findings From a National Study. J Nutr Educ Behav. 2017;49(1):67-72.e1. [PubMed]

62.

Haghighatdoost F, Kelishadi R, Qorbani M, et al. Family Dinner Frequency is Inversely Related to Mental Disorders and Obesity in Adolescents: the CASPIAN-III Study. Arch Iran Med. 2017;20(4):218-223. [PubMed]

63.

Frank S, Dahler L, Santurri LE, Knight K. Hyper-texting and hyper-networking: A new health risk category for teens? ResearchGate. https://www.researchgate.net/publication/266901685_Hyper-texting_and_hyper-networking_A_new_health_risk_category_for_teens. Published May 30, 2017. Accessed June 2, 2017.

64.

Late-night texting detrimental to adolescent mental health. Mental Health Today. https://www.mentalhealthtoday.co.uk/latenight_texting_detrimental_to_adolescent_mental_health_25769840187.aspx. Published May 31, 2017. Accessed June 2, 2017.

65.

Campbell D, Felker B, Liu C, et al. Prevalence of Depression–PTSD Comorbidity: Implications for Clinical Practice Guidelines and Primary Care-based Interventions. J Gen Intern Med. 2007;22(6):711-718. [PMC]

66.

Rytwinski N, Scur M, Feeny N, Youngstrom E. The co-occurrence of major depressive disorder among individuals with posttraumatic stress disorder: a meta-analysis. J Trauma Stress. 2013;26(3):299-309. [PubMed]

67.

Stolove C, Galatzer-Levy I, Bonanno G. Emergence of depression following job loss prospectively predicts lower rates of reemployment. Psychiatry Res. 2017;253:79-83. [PubMed]

68.

Kaltiala-Heino R, Fröjd S. Correlation between bullying and clinical depression in adolescent patients. Adolesc Health Med Ther. 2011;2:37-44. [PMC]

69.

Hagen EH. The Functions of Postpartum Depression. E. 1999;20(5):325-359. doi:10.1016/s1090-5138(99)00016-1

70.

Mota Pereira J, Fonte D. Pets enhance antidepressant pharmacotherapy effects in patients with treatment resistant major depressive disorder. J. 2018;104:108-113. doi:10.1016/j.jpsychires.2018.07.004

71.

Bratman G, Hamilton J, Hahn K, Daily G, Gross J. Nature experience reduces rumination and subgenual prefrontal cortex activation. Proc Natl Acad Sci U S A. 2015;112(28):8567-8572. [PubMed]

72.

Berman M, Kross E, Krpan K, et al. Interacting with nature improves cognition and affect for individuals with depression. J Affect Disord. 2012;140(3):300-305. [PubMed]

73.

Lederbogen F, Kirsch P, Haddad L, et al. City living and urban upbringing affect neural social stress processing in humans. Nature. 2011;474(7352):498-501. [PubMed]

74.

Stress in the city: Brain activity and biology behind mood disorders of urbanites. ScienceDaily. https://www.sciencedaily.com/releases/2011/06/110622135216.htm. Published June 23, 2011. Accessed February 7, 2017.

75.

Soga M, Gaston K, Yamaura Y. Gardening is beneficial for health: A meta-analysis. Prev Med Rep. 2016;5:92-99. [PMC]

76.

Nutsford D, Pearson A, Kingham S, Reitsma F. Residential exposure to visible blue space (but not green space) associated with lower psychological distress in a capital city. Health Place. 2016;39:70-78. [PubMed]

77.

Martyn P, Brymer E. The relationship between nature relatedness and anxiety. J Health Psychol. 2016;21(7):1436-1445. [PubMed]

78.

van den Berg M, Wendel-Vos W, van Poppel M, Kemper H, van Mechelen W, Maas J. Health benefits of green spaces in the living environment: A systematic review of epidemiological studies. Urban Forestry & Urban Greening. 2015;14(4):806-816. doi:10.1016/j.ufug.2015.07.008

79.

de Vries S, ten Have M, van Dorsselaer S, van Wezep M, Hermans T, de Graaf R. Local availability of green and blue space and prevalence of common mental disorders in the Netherlands. Br J Psychiatry Open. 2016;2(6):366-372. doi:10.1192/bjpo.bp.115.002469

80.

Barton J, Pretty J. What is the best dose of nature and green exercise for improving mental health? A multi-study analysis. Environ Sci Technol. 2010;44(10):3947-3955. [PubMed]

81.

Netz Y. Is the Comparison between Exercise and Pharmacologic Treatment of Depression in the Clinical Practice Guideline of the American College of Physicians Evidence-Based? Front Pharmacol. 2017;8:257. [PMC]

82.

Harvey S, Øverland S, Hatch S, Wessely S, Mykletun A, Hotopf M. Exercise and the Prevention of Depression: Results of the HUNT Cohort Study. Am J Psychiatry. October 2017:appiajp201716111223. [PubMed]

83.

Silveira H, Moraes H, Oliveira N, Coutinho E, Laks J, Deslandes A. Physical exercise and clinically depressed patients: a systematic review and meta-analysis. Neuropsychobiology. 2013;67(2):61-68. [PubMed]

84.

Trivedi M, Greer T, Church T, et al. Exercise as an augmentation treatment for nonremitted major depressive disorder: a randomized, parallel dose comparison. J Clin Psychiatry. 2011;72(5):677-684. [PubMed]

85.

Balasubramaniam M, Telles S, Doraiswamy P. Yoga on our minds: a systematic review of yoga for neuropsychiatric disorders. Front Psychiatry. 2013;3:117. [PubMed]

86.

Rosmarin D, Bigda-Peyton J, Kertz S, Smith N, Rauch S, Björgvinsson T. A test of faith in God and treatment: the relationship of belief in God to psychiatric treatment outcomes. J Affect Disord. 2013;146(3):441-446. [PubMed]

87.

Johnstone B, Yoon D, Cohen D, et al. Relationships among spirituality, religious practices, personality factors, and health for five different faith traditions. J Relig Health. 2012;51(4):1017-1041. [PubMed]

88.

Raes F, Smets J, Wessel I, et al. Turning the pink cloud grey: dampening of positive affect predicts postpartum depressive symptoms. J Psychosom Res. 2014;77(1):64-69. [PubMed]

89.

Ford B, Lam P, John O, Mauss I. The Psychological Health Benefits of Accepting Negative Emotions and Thoughts: Laboratory, Diary, and Longitudinal Evidence. J Pers Soc Psychol. July 2017. [PubMed]

90.

Gračanin A, Vingerhoets A, Kardum I, Zupčić M, Šantek M, Šimić M. Why crying does and sometimes does not seem to alleviate mood: a quasi-experimental study. Motiv Emot. 2015;39(6):953-960. [PubMed]

91.

Read J, Cartwright C, Gibson K. Adverse emotional and interpersonal effects reported by 1829 New Zealanders while taking antidepressants. Psychiatry Res. 2014;216(1):67-73. [PubMed]

92.

Baker D, Algorta G. The Relationship Between Online Social Networking and Depression: A Systematic Review of Quantitative Studies. Cyberpsychol Behav Soc Netw. 2016;19(11):638-648. [PubMed]

93.

Seabrook E, Kern M, Rickard N. Social Networking Sites, Depression, and Anxiety: A Systematic Review. JMIR Ment Health. 2016;3(4):e50. [PubMed]

94.

Tromholt M. The Facebook Experiment: Quitting Facebook Leads to Higher Levels of Well-Being. Cyberpsychol Behav Soc Netw. 2016;19(11):661-666. [PubMed]

95.

Shakya H, Christakis N. Association of Facebook Use With Compromised Well-Being: A Longitudinal Study. Am J Epidemiol. 2017;185(3):203-211. [PubMed]

96.

Roberts JA, David ME. My life has become a major distraction from my cell phone: Partner phubbing and relationship satisfaction among romantic partners. Computers in Human Behavior. 2016;54:134-141. doi:10.1016/j.chb.2015.07.058

97.

Panova T, Lleras A. Avoidance or boredom: Negative mental health outcomes associated with use of Information and Communication Technologies depend on users’ motivations. Computers in Human Behavior. 2016;58:249-258. doi:10.1016/j.chb.2015.12.062

98.

Virtanen M, Stansfeld S, Fuhrer R, Ferrie J, Kivimäki M. Overtime work as a predictor of major depressive episode: a 5-year follow-up of the Whitehall II study. PLoS One. 2012;7(1):e30719. [PubMed]

99.

Bianchi R, Schonfeld IS, Laurent E. Is burnout a depressive disorder? A reexamination with special focus on atypical depression. International Journal of Stress Management. 2014;21(4):307-324. doi:10.1037/a0037906

100.

Dinh H, Strazdins L, Welsh J. Hour-glass ceilings: Work-hour thresholds, gendered health inequities. Social Science & Medicine. 2017;176:42-51. doi:10.1016/j.socscimed.2017.01.024

101.

Irwin MR. Why Sleep Is Important for Health: A Psychoneuroimmunology Perspective. A. 2015;66(1):143-172. doi:10.1146/annurev-psych-010213-115205

102.

Tang NKY, Fiecas M, Afolalu EF, Wolke D. Changes in Sleep Duration, Quality, and Medication Use Are Prospectively Associated With Health and Well-being: Analysis of the UK Household Longitudinal Study. Sleep. 2017;40(3). doi:10.1093/sleep/zsw079

103.

Johnson E, Roth T, Breslau N. The association of insomnia with anxiety disorders and depression: exploration of the direction of risk. J Psychiatr Res. 2006;40(8):700-708. [PubMed]

104.

Kaminski-Hartenthaler A, Nussbaumer B, Forneris C, et al. Melatonin and agomelatine for preventing seasonal affective disorder. Cochrane Database Syst Rev. 2015;(11):CD011271. [PubMed]

105.

Hansen M, Danielsen A, Hageman I, Rosenberg J, Gögenur I. The therapeutic or prophylactic effect of exogenous melatonin against depression and depressive symptoms: a systematic review and meta-analysis. Eur Neuropsychopharmacol. 2014;24(11):1719-1728. [PubMed]

106.

Lam R, Levitt A, Levitan R, et al. Efficacy of Bright Light Treatment, Fluoxetine, and the Combination in Patients With Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2016;73(1):56-63. [PubMed]

107.

aan het, Benkelfat C, Boivin D, Young S. Bright light exposure during acute tryptophan depletion prevents a lowering of mood in mildly seasonal women. Eur Neuropsychopharmacol. 2008;18(1):14-23. [PubMed]

108.

Virk G, Reeves G, Rosenthal N, Sher L, Postolache T. Short exposure to light treatment improves depression scores in patients with seasonal affective disorder: A brief report. Int J Disabil Hum Dev. 2009;8(3):283-286. [PubMed]

109.

Reeves G, Nijjar G, Langenberg P, et al. Improvement in depression scores after 1 hour of light therapy treatment in patients with seasonal affective disorder. J Nerv Ment Dis. 2012;200(1):51-55. [PubMed]

110.

Gloth F, Alam W, Hollis B. Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder. J Nutr Health Aging. 1999;3(1):5-7. [PubMed]

111.

Carey B. Sleep Therapy Seen as an Aid for Depression. The New York Times. http://www.nytimes.com/2013/11/19/health/treating-insomnia-to-heal-depression.html. Published November 18, 2013. Accessed February 7, 2017.

112.

Manber R, Edinger J, Gress J, San P-S, Kuo T, Kalista T. Cognitive behavioral therapy for insomnia enhances depression outcome in patients with comorbid major depressive disorder and insomnia. Sleep. 2008;31(4):489-495. [PubMed]

113.

Edwards C, Mukherjee S, Simpson L, Palmer L, Almeida O, Hillman D. Depressive Symptoms before and after Treatment of Obstructive Sleep Apnea in Men and Women. J Clin Sleep Med. 2015;11(9):1029-1038. [PubMed]

114.

CDC Study Shows Association Between Depression and Sleep Apnea. National Sleep Foundation. https://sleepfoundation.org/sleep-news/cdc-study-shows-association-between-depression-and-sleep-apnea. Accessed February 7, 2017.

115.

Chan M, Wong Z, Thayala N. The effectiveness of music listening in reducing depressive symptoms in adults: a systematic review. Complement Ther Med. 2011;19(6):332-348. [PubMed]

116.

Coronado-Montoya S, Levis A, Kwakkenbos L, Steele R, Turner E, Thombs B. Reporting of Positive Results in Randomized Controlled Trials of Mindfulness-Based Mental Health Interventions. PLoS One. 2016;11(4):e0153220. [PubMed]

117.

Van D, van V, Vago D, et al. Mind the Hype: A Critical Evaluation and Prescriptive Agenda for Research on Mindfulness and Meditation. Perspect Psychol Sci. September 2017:1745691617709589. [PubMed]

118.

Alderman B, Olson R, Brush C, Shors T. MAP training: combining meditation and aerobic exercise reduces depression and rumination while enhancing synchronized brain activity. Transl Psychiatry. 2016;6:e726. [PubMed]

119.

Wang F, Lee E, Wu T, et al. The effects of tai chi on depression, anxiety, and psychological well-being: a systematic review and meta-analysis. Int J Behav Med. 2014;21(4):605-617. [PubMed]

120.

Fancourt D, Perkins R, Ascenso S, Carvalho L, Steptoe A, Williamon A. Effects of Group Drumming Interventions on Anxiety, Depression, Social Resilience and Inflammatory Immune Response among Mental Health Service Users. PLoS One. 2016;11(3):e0151136. [PubMed]

121.

Lavretsky H, Epel E, Siddarth P, et al. A pilot study of yogic meditation for family dementia caregivers with depressive symptoms: effects on mental health, cognition, and telomerase activity. Int J Geriatr Psychiatry. 2013;28(1):57-65. [PubMed]

122.

Brogan, MD K. Change Your Life in 12 Minutes a Day. Kelly Brogan MD. http://kellybroganmd.com/change-your-life-in-12-minutes-a-day/. Published December 30, 2016. Accessed February 7, 2017.

123.

Katerndahl D, Bell I, Palmer R, Miller C. Chemical intolerance in primary care settings: prevalence, comorbidity, and outcomes. Ann Fam Med. 2012;10(4):357-365. [PubMed]

124.

Potera C. Mental Health: Molding a Link to Depression. Environ Health Perspect. 2007;115(11):A536. [PMC]

125.

Walton R, Hudak R, Green-Waite R. Adverse reactions to aspartame: double-blind challenge in patients from a vulnerable population. Biol Psychiatry. 1993;34(1-2):13-17. [PubMed]

126.

Kern J, Geier D, Bjørklund G, et al. Evidence supporting a link between dental amalgams and chronic illness, fatigue, depression, anxiety, and suicide. Neuro Endocrinol Lett. 2014;35(7):537-552. [PubMed]

127.

Siblerud R, Motl J, Kienholz E. Psychometric evidence that mercury from silver dental fillings may be an etiological factor in depression, excessive anger, and anxiety. Psychol Rep. 1994;74(1):67-80. [PubMed]

128.

Wojcik D, Godfrey M, Christie D, Haley B. Mercury toxicity presenting as chronic fatigue, memory impairment and depression: diagnosis, treatment, susceptibility, and outcomes in a New Zealand general practice setting (1994-2006). Neuro Endocrinol Lett. 2006;27(4):415-423. [PubMed]

129.

Malt U, Nerdrum P, Oppedal B, Gundersen R, Holte M, Löne J. Physical and mental problems attributed to dental amalgam fillings: a descriptive study of 99 self-referred patients compared with 272 controls. Psychosom Med. 1997;59(1):32-41. [PubMed]

130.

Siblerud R. A comparison of mental health of multiple sclerosis patients with silver/mercury dental fillings and those with fillings removed. Psychol Rep. 1992;70(3 Pt 2):1139-1151. [PubMed]

131.

El-Essawy H. Depression and Other Neurotransmitter Related Conditions: The Mercury Connection. DAMS – Dental Amalgam Mercury Solutions. http://amalgam.org/education/scientific-evidenceresearch/depression-neurotransmitter-related-conditions-mercury-connection/. Accessed February 7, 2017.

132.

Soleo L, Urbano M, Petrera V, Ambrosi L. Effects of low exposure to inorganic mercury on psychological performance. Br J Ind Med. 1990;47(2):105-109. [PubMed]

133.

Mutter J. Is dental amalgam safe for humans? The opinion of the scientific committee of the European Commission. J Occup Med Toxicol. 2011;6(1):2. [PubMed]

134.

Reuben A, Schaefer JD, Moffitt TE, et al. Association of Childhood Lead Exposure With Adult Personality Traits and Lifelong Mental Health. J. 2019;76(4):418. doi:10.1001/jamapsychiatry.2018.4192

135.

Hemenway D, Solnick S, Colditz G. Smoking and suicide among nurses. Am J Public Health. 1993;83(2):249-251. [PubMed]

136.

Miller M, Hemenway D, Rimm E. Cigarettes and suicide: a prospective study of 50,000 men. Am J Public Health. 2000;90(5):768-773. [PubMed]

137.

Miller M, Hemenway D, Bell N, Yore M, Amoroso P. Cigarette smoking and suicide: a prospective study of 300,000 male active-duty Army soldiers. Am J Epidemiol. 2000;151(11):1060-1063. [PubMed]

138.

Iwasaki M, Akechi T, Uchitomi Y, Tsugane S, Japan P. Cigarette smoking and completed suicide among middle-aged men: a population-based cohort study in Japan. Ann Epidemiol. 2005;15(4):286-292. [PubMed]

139.

Bronisch T, Höfler M, Lieb R. Smoking predicts suicidality: findings from a prospective community study. J Affect Disord. 2008;108(1-2):135-145. [PubMed]

140.

Boden J, Fergusson D, Horwood L. Cigarette smoking and depression: tests of causal linkages using a longitudinal birth cohort. Br J Psychiatry. 2010;196(6):440-446. [PubMed]

141.

Richter P, Bishop E, Wang J, Kaufmann R. Trends in Tobacco Smoke Exposure and Blood Lead Levels Among Youths and Adults in the United States: The National Health and Nutrition Examination Survey, 1999–2008. Prev Chronic Dis. 2013;10:E213. [PMC]

142.

Jung SY, Kim S, Lee K, et al. Association between secondhand smoke exposure and blood lead and cadmium concentration in community dwelling women: the fifth Korea National Health and Nutrition Examination Survey (2010–2012). B. 2015;5(7):e008218. doi:10.1136/bmjopen-2015-008218

143.

Taylor G, McNeill A, Girling A, Farley A, Lindson-Hawley N, Aveyard P. Change in mental health after smoking cessation: systematic review and meta-analysis. BMJ. 2014;348:g1151. [PMC]

144.

Stallones L, Beseler C. Pesticide poisoning and depressive symptoms among farm residents. Ann Epidemiol. 2002;12(6):389-394. [PubMed]

145.

Beseler C, Stallones L. A cohort study of pesticide poisoning and depression in Colorado farm residents. Ann Epidemiol. 2008;18(10):768-774. [PubMed]

146.

Beseler C, Stallones L, Hoppin J, et al. Depression and pesticide exposures among private pesticide applicators enrolled in the Agricultural Health Study. Environ Health Perspect. 2008;116(12):1713-1719. [PubMed]

147.

Zhang J, Stewart R, Phillips M, Shi Q, Prince M. Pesticide exposure and suicidal ideation in rural communities in Zhejiang province, China. Bull World Health Organ. 2009;87(10):745-753. [PubMed]

148.

Weisskopf M, Moisan F, Tzourio C, Rathouz P, Elbaz A. Pesticide exposure and depression among agricultural workers in France. Am J Epidemiol. 2013;178(7):1051-1058. [PubMed]

149.

Faria N, Fassa A, Meucci R. Association between pesticide exposure and suicide rates in Brazil. Neurotoxicology. 2014;45:355-362. [PubMed]

150.

Beard J, Umbach D, Hoppin J, et al. Pesticide exposure and depression among male private pesticide applicators in the agricultural health study. Environ Health Perspect. 2014;122(9):984-991. [PubMed]

151.

Bienkowski,Environmental Health News B. High Rates of Suicide, Depression Linked to Farmers’ Use of Pesticides. Scientific American. http://www.scientificamerican.com/article/high-rates-of-suicide-depression-linked-to-farmers-use-of-pesticides/. Published October 6, 2014. Accessed February 7, 2017.

152.

Power M, Kioumourtzoglou M, Hart J, Okereke O, Laden F, Weisskopf M. The relation between past exposure to fine particulate air pollution and prevalent anxiety: observational cohort study. BMJ. 2015;350:h1111. [PubMed]

153.

Sass V, Kravitz-Wirtz N, Karceski SM, Hajat A, Crowder K, Takeuchi D. The effects of air pollution on individual psychological distress. H. 2017;48:72-79. doi:10.1016/j.healthplace.2017.09.006

154.

Orban E, McDonald K, Sutcliffe R, et al. Residential Road Traffic Noise and High Depressive Symptoms after Five Years of Follow-up: Results from the Heinz Nixdorf Recall Study. Environ Health Perspect. 2016;124(5):578-585. [PubMed]

155.

Beutel M, Jünger C, Klein E, et al. Noise Annoyance Is Associated with Depression and Anxiety in the General Population- The Contribution of Aircraft Noise. PLoS One. 2016;11(5):e0155357. [PMC]

156.

Perera F, Nolte E, Wang Y, et al. Bisphenol A exposure and symptoms of anxiety and depression among inner city children at 10-12 years of age. Environ Res. 2016;151:195-202. [PubMed]

157.

Scherrer J, Svrakic D, Freedland K, et al. Prescription opioid analgesics increase the risk of depression. J Gen Intern Med. 2014;29(3):491-499. [PubMed]

158.

Ried L, Tueth M, Handberg E, Kupfer S, Pepine C, INVEST S. A Study of Antihypertensive Drugs and Depressive Symptoms (SADD-Sx) in patients treated with a calcium antagonist versus an atenolol hypertension Treatment Strategy in the International Verapamil SR-Trandolapril Study (INVEST). Psychosom Med. 2005;67(3):398-406. [PubMed]

159.

Boal AH, Smith DJ, McCallum L, et al. Monotherapy With Major Antihypertensive Drug Classes and Risk of Hospital Admissions for Mood DisordersNovelty and Significance. Hypertension. 2016;68(5):1132-1138. doi:10.1161/hypertensionaha.116.08188

160.

Zipursky JS, Macdonald EM, Luo J, et al. Lipophilic β-Blockers and Suicide in the Elderly. J. 2017;37(3):381-384. doi:10.1097/jcp.0000000000000695

161.

Skovlund C, Mørch L, Kessing L, Lidegaard Ø. Association of Hormonal Contraception With Depression. JAMA Psychiatry. 2016;73(11):1154-1162. [PubMed]

162.

Skovlund C, Mørch L, Kessing L, Lange T, Lidegaard Ø. Association of Hormonal Contraception With Suicide Attempts and Suicides. Am J Psychiatry. 2018;175(4):336-342. [PubMed]

163.

You H, Lu W, Zhao S, Hu Z, Zhang J. The relationship between statins and depression: a review of the literature. Expert Opin Pharmacother. 2013;14(11):1467-1476. [PubMed]

164.

Kunugi H, Takei N, Aoki H, Nanko S. Low serum cholesterol in suicide attempters. Biol Psychiatry. 1997;41(2):196-200. [PubMed]

165.

Engelberg H. Low serum cholesterol and suicide. Lancet. 1992;339(8795):727-729. [PubMed]

166.

Glueck C, Tieger M, Kunkel R, Hamer T, Tracy T, Speirs J. Hypocholesterolemia and affective disorders. Am J Med Sci. 1994;308(4):218-225. [PubMed]

167.

Suarez E. Relations of trait depression and anxiety to low lipid and lipoprotein concentrations in healthy young adult women. Psychosom Med. 1999;61(3):273-279. [PubMed]

168.

Qato DM, Ozenberger K, Olfson M. Prevalence of Prescription Medications With Depression as a Potential Adverse Effect Among Adults in the United States. J. 2018;319(22):2289. doi:10.1001/jama.2018.6741

169.

Henriksen T, Skrede S, Fasmer O, et al. Blue-blocking glasses as additive treatment for mania: a randomized placebo-controlled trial. Bipolar Disord. 2016;18(3):221-232. [PubMed]

170.

Obayashi K, Saeki K, Kurumatani N. Bedroom Light Exposure at Night and the Incidence of Depressive Symptoms: A Longitudinal Study of the HEIJO-KYO Cohort. American Journal of Epidemiology. 2017;187(3):427-434. doi:10.1093/aje/kwx290

171.

Bedrosian T, Weil Z, Nelson R. Chronic dim light at night provokes reversible depression-like phenotype: possible role for TNF. Mol Psychiatry. 2013;18(8):930-936. [PubMed]

172.

Obayashi K, Saeki K, Iwamoto J, Ikada Y, Kurumatani N. Exposure to light at night and risk of depression in the elderly. J Affect Disord. 2013;151(1):331-336. [PubMed]

173.

Pall ML. Microwave frequency electromagnetic fields (EMFs) produce widespread neuropsychiatric effects including depression. Journal of Chemical Neuroanatomy. 2016;75:43-51. doi:10.1016/j.jchemneu.2015.08.001

174.

Gøtzsche P, Gøtzsche P. Cognitive behavioural therapy halves the risk of repeated suicide attempts: systematic review. J R Soc Med. 2017;110(10):404-410. [PMC]

175.

A Mind of Your Own by Kelly Brogan MD. Kelly Brogan MD. http://kellybroganmd.com/amindofyourown/. Accessed February 7, 2017.

Depression – Roles of Infection, Stress, and Toxicants